Lyme Arthritis Treatment: Methotrexate, DMARDs, and Persistent Symptoms
Lyme arthritis treatment can be challenging
Persistent joint symptoms may have more than one explanation
Antibiotics, DMARDs, and shared decision-making require caution
Lyme arthritis treatment becomes more complicated when joint symptoms persist after antibiotic therapy. Some patients may have ongoing infection, some may have post-infectious inflammation, and others may have another inflammatory arthritis such as rheumatoid arthritis or psoriatic arthritis.
Disease-modifying antirheumatic drugs (DMARDs) are intended to slow inflammatory disease progression. Synthetic DMARDs include methotrexate and sulfasalazine. Biological DMARDs include infliximab, anakinra, rituximab, and abatacept.
This article reviews factors to consider when persistent Lyme arthritis symptoms raise questions about antibiotics, inflammation, autoimmune disease, or the role of DMARD treatment.
For a broader overview, see Lyme arthritis.
What is Lyme arthritis?
Lyme arthritis is an inflammatory complication of Lyme disease that commonly affects large joints, particularly the knee, and may persist even after treatment in some patients.
Arthritis due to Lyme disease can resemble autoimmune arthritis, making diagnosis difficult when joint symptoms persist after treatment.
The treatment dilemma in Lyme arthritis
I can agree with the conundrum raised by Dr. Steere in the Journal of Rheumatology:
- “Do [Lyme arthritis] patients with little or no apparent response to oral antibiotic therapy still have active B. burgdorferi infection requiring IV antibiotic therapy…
- Do they have post-infectious Lyme arthritis requiring therapy with disease-modifying antirheumatic drugs…
- Or do they have another form of chronic inflammatory arthritis?” ¹
The wrong treatment could have detrimental effects, as Steere points out. “Either IV antibiotics or DMARD, given inappropriately, might be harmful.”
Antibiotics, inflammation, or another arthritis?
I do not agree, however, with Dr. Steere’s conclusion: “It is now clear that this complication is not caused by antibiotic resistance or failure of spirochetal killing.”
Furthermore, I do not agree with his approach: “We treat these patients with DMARD such as hydroxychloroquine, methotrexate, or tumor necrosis factor inhibitors, the standard of care for other forms of chronic inflammatory arthritis.”
Both treatment approaches have limitations.
Antibiotics may lead to adverse events including diarrhea due to C. difficile, concerns regarding antibiotic resistance, or delays in DMARD treatment when inflammatory arthritis is driving symptoms.
Meanwhile, DMARDs have their own side effects and may contribute to treatment failures if they delay antibiotic treatment in patients with unresolved infection.¹
Treatment for Lyme arthritis typically begins with antibiotics, but persistent symptoms may require reassessment for ongoing infection, inflammatory arthritis, or other causes.
Methotrexate for Lyme disease remains controversial
The evidence supporting methotrexate and other DMARDs in Lyme disease patients remains limited.
Evidence supporting DMARD use is primarily based on case series rather than randomized clinical trials. Doctors at Massachusetts General Hospital described a series of 30 patients who developed systemic autoimmune joint disease following Lyme disease.
“Fifteen had rheumatoid arthritis (RA), 13 had psoriatic arthritis (PsA), and 2 had peripheral spondyloarthropathy (SpA),” according to Arvikar and colleagues.² They reported that DMARD treatment reduced pain in these patients.
However, the study was not designed to determine whether DMARD treatment addressed other manifestations including fatigue, neuropathy, neuropsychiatric symptoms, or Lyme encephalopathy.
Lyme arthritis vs rheumatoid arthritis
Patients frequently ask whether Lyme disease can cause rheumatoid arthritis or whether Lyme arthritis can mimic rheumatoid arthritis.
Lyme arthritis more commonly affects large joints such as the knee. Rheumatoid arthritis more often affects smaller joints in a symmetric pattern involving hands and wrists, although overlap can occur.
Hand arthritis can occur in many inflammatory conditions, but Lyme arthritis more often presents with large-joint swelling. When hand symptoms dominate, rheumatoid arthritis or another inflammatory arthritis should remain in the differential diagnosis.
When arthritis follows Lyme disease, doctors should consider persistent infection, post-infectious inflammation, Lyme-triggered autoimmune disease, or an unrelated inflammatory arthritis emerging at the same time.
For patients with persistent symptoms after treatment, see persistent Lyme disease symptoms.
For symptom context, see Lyme disease symptoms guide.
Shared decision-making before DMARD treatment
It is important for doctors to be confident that persistent infection has been addressed before prescribing DMARDs to patients with systemic autoimmune joint disease after Lyme disease.
It is also reasonable to include patients in the discussion when prescribing DMARDs, allowing shared decision-making about risks, benefits, uncertainty, and treatment goals.
Frequently Asked Questions
What is Lyme arthritis treatment?
Lyme arthritis treatment typically begins with antibiotic therapy, but persistent joint swelling may require reassessment for ongoing infection, post-infectious inflammation, or another inflammatory arthritis.
Is methotrexate used for Lyme arthritis?
Methotrexate is sometimes used when persistent inflammatory arthritis is believed to be post-infectious or autoimmune, but its role in Lyme disease remains controversial.
Can Lyme arthritis be cured?
Many patients improve with appropriate antibiotic treatment, but persistent joint inflammation may require reassessment for ongoing infection, post-infectious inflammation, or another arthritis diagnosis.
What is antibiotic-refractory Lyme arthritis?
Antibiotic-refractory Lyme arthritis refers to persistent joint inflammation after antibiotic treatment, though the cause may vary and remains debated.
How is Lyme arthritis different from rheumatoid arthritis?
Lyme arthritis often affects large joints such as the knee, while rheumatoid arthritis more commonly causes symmetric small-joint inflammation, although overlap can occur.
Clinical Takeaway
Lyme arthritis treatment becomes more difficult when joint symptoms persist after antibiotics.
Some patients may have ongoing infection, some may have post-infectious inflammation, and others may have another inflammatory arthritis such as rheumatoid arthritis, psoriatic arthritis, or spondyloarthropathy.
Before prescribing methotrexate or other DMARDs, clinicians should carefully reassess whether persistent infection has been adequately addressed and involve patients in shared decision-making.
Related Articles
Autoimmune joint disease after Lyme disease
Can Lyme disease trigger autoimmune disease?
Persistent infection or inflammatory immune response?
References
- Steere AC. Treatment of Lyme Arthritis. J Rheumatol. 2019;46(8):871-873.
- Arvikar SL, Crowley JT, Sulka KB, Steere AC. Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthropathy, Following Lyme Disease. Arthritis & Rheumatology. 2016.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
